tbuckley/cabot-search huggingface dataset:
Risk Factors for Severe Seafood Allergy in an Urban City in Vietnam
Authors: Tu Trinh, Chi Duong, Tu Pham, Trung Hao Au, Loc Tran, Loc Tran, Cuong Nguyen, Han Nguyen, Nguyen Tran, Quy Phan, Thu Le, Thu Le, Duy Pham, Tai Tran
Journal: Journal of Allergy and Clinical Immunology (2023)
Cross-Reactive Shellfish-specific Monoclonal IgE Antibodies Discovered from Highly Allergic Individuals
Authors: Ben Chung, Joyce Wong, Venu Aruva, Paige Creeks, Johanna Romero, Saba Sohail, Eric Mabery, Anmoldeep Kaur, Roger Thomas, Henry Lowman, Derek Croote
Journal: Journal of Allergy and Clinical Immunology (2023)
Modulation of Pro-Allergic T Cell Responses by PQ Grass 27600 SU as a Treatment for Seasonal Allergic Rhinitis: A RDBPC Pilot Study
Authors: Janice Layhadi, Lily Wu, Paulina Filipaviciute, Kemi Oluwayi, Sviatlana Starchenka, Olesya Rusyn, Oliver Armfield, Katarzyna Lis, Matthias Kramer, Matthew Heath, Murray Skinner, Pieter-Jan de Kam, Mohamed Shamji
Journal: Journal of Allergy and Clinical Immunology (2023)
Expression of Heat Shock Proteins in PBMCs is Altered Upon Exposure to Hypothermic and Hyperthermic Conditions and is Correlated with NF-kB Expression
Authors: Jackson Schuetz, Diane Dunham, Xiaoying Zhou, Hana Seastedt, Ravina Nath, Rosemarie DeKruyff, Mary Prunicki, Kari Nadeau
Journal: Journal of Allergy and Clinical Immunology (2023)
The hippo kinases MST1/2 in cardiovascular and metabolic diseases: A promising therapeutic target option for pharmacotherapy
Authors: Yunfei Yin, Mingyue Tan, Lianhua Han, Lei Zhang, Yue Zhang, Jun Zhang, Wanqian Pan, Jiaxiang Bai, Tingbo Jiang, Hongxia Li
Journal: Acta Pharmaceutica Sinica B (2023)

Cardiovascular diseases (CVDs) and metabolic disorders are major components of noncommunicable diseases, causing an enormous health and economic burden worldwide. There are common risk factors and developmental mechanisms among them, indicating the far-reaching significance in exploring the corresponding therapeutic targets. MST1/2 kinases are well-established proapoptotic effectors that also bidirectionally regulate autophagic activity. Recent studies have demonstrated that MST1/2 influence the outcome of cardiovascular and metabolic diseases by regulating immune inflammation. In addition, drug development against them is in full swing. In this review, we mainly describe the roles and mechanisms of MST1/2 in apoptosis and autophagy in cardiovascular and metabolic events as well as emphasis on the existing evidence for their involvement in immune inflammation. Moreover, we summarize the latest progress of pharmacotherapy targeting MST1/2 and propose a new mode of drug combination therapy, which may be beneficial to seek more effective strategies to prevent and treat CVDs and metabolic disorders.
Distribution and Detectability of EGFR Exon 20 Insertion Variants in NSCLC
Authors: Sai-Hong Ignatius Ou, Jin-Liern Hong, Petros Christopoulos, Huamao M. Lin, Sylvie Vincent, Eric N. Churchill, Junpei Soeda, Daniel Kazdal, Albrecht Stenzinger, Michael Thomas
Journal: Journal of Thoracic Oncology (2023)

EGFR exon 20 insertion (ex20ins) mutations represent 5% to 10% of EGFR mutations in NSCLC. Identifying patients with EGFR ex20ins is challenging owing to the limited coverage of polymerase chain reaction (PCR) assays and the relatively recent use of next-generation sequencing (NGS). This study analyzes the spectrum of EGFR ex20ins variants in a large patient population from a global clinical trial and several real-world cohorts and the ability of PCR kits to identify these alterations.We conducted this retrospective analysis in patients with NSCLC who underwent NGS or other sequencing testing and had a known EGFR ex20ins mutation. Patients were gathered from a clinical trial (NCT02716116), a chart review study in Germany, and the LC-SCRUM-Japan, GENIE, and U.S. COTA databases. Proportions of patients with ex20ins variants that could have been detected by six commercially available and widely used PCR kits were calculated in each data set.Overall, 636 patients with NSCLC harboring EGFR ex20ins mutations were included in this analysis and 104 unique EGFR ex20ins variants were identified across the data sources. The proportion of patients whose ex20ins could have been detected by any PCR test alone ranged from 11.8% to 58.9% across the data sources.Our findings suggest that the PCR tests evaluated would have missed more than 40% of patients with NSCLC harboring EGFR ex20ins mutations. NGS-based genetic testing is preferable than standard PCR assays and can substantially improve the identification of the diverse profile of EGFR ex20ins variants in NSCLC.
Demystifying the Results of RTOG 0617: Identification of Dose Sensitive Cardiac Subregions Associated With Overall Survival
Authors: Alan McWilliam, Azadeh Abravan, Kathryn Banfill, Corinne Faivre-Finn, Marcel van Herk
Journal: Journal of Thoracic Oncology (2023)

The RTOG 0617 trial presented a worse survival for patients with lung cancer treated in the high-dose (74 Gy) arm. In multivariable models, radiation level and whole-heart volumetric dose parameters were associated with survival. In this work, we consider heart subregions to explain the observed survival difference between radiation levels.
A human liver organoid screening platform for DILI risk prediction
Authors: Charles J. Zhang, Sophia R. Meyer, Matthew J. O’Meara, Sha Huang, Meghan M. Capeling, Daysha Ferrer-Torres, Charlie J. Childs, Jason R. Spence, Robert J. Fontana, Jonathan Z. Sexton
Journal: Journal of Hepatology (2023)

Drug-induced liver injury (DILI), both intrinsic and idiosyncratic, causes frequent morbidity, mortality, clinical trial failures and post-approval withdrawal. This suggests an unmet need for improved in vitro models for DILI risk prediction that can account for diverse host genetics and other clinical factors. In this study, we evaluated the utility of human liver organoids (HLOs) for high-throughput DILI risk prediction and in an organ-on-chip system.
Identification of disease-related aberrantly spliced transcripts in myeloma and strategies to target these alterations by RNA-based therapeutics
Authors: Daisuke Ogiya, Zuzana Chyra, Sigitas J Verselis, Morgan O'Keefe, Jacquelyn Cobb, Ivane Abiatari, Srikanth Talluri, Anjana Anilkumar Sithara, Teru Hideshima, Michael P Chu, Roman Hájek, David M Dorfman, Linda M Pilarski, Kenneth C Anderson, Sophia Adamia
Journal: Blood Cancer Journal (2023)

Abstract Novel drug discoveries have shifted the treatment paradigms of most hematological malignancies, including multiple myeloma (MM). However, this plasma cell malignancy remains incurable, and novel therapies are therefore urgently needed. Whole-genome transcriptome analyses in a large cohort of MM patients demonstrated that alterations in pre-mRNA splicing (AS) are frequent in MM. This manuscript describes approaches to identify disease-specific alterations in MM and proposes RNA-based therapeutic strategies to eradicate such alterations. As a “proof of concept”, we examined the causes of aberrant HMMR (Hyaluronan-mediated motility receptor) splicing in MM. We identified clusters of single nucleotide variations (SNVs) in the HMMR transcript where the altered splicing took place. Using bioinformatics tools, we predicted SNVs and splicing factors that potentially contribute to aberrant HMMR splicing. Based on bioinformatic analyses and validation studies, we provided the rationale for RNA-based therapeutic strategies to selectively inhibit altered HMMR splicing in MM. Since splicing is a hallmark of many cancers, strategies described herein for target identification and the design of RNA-based therapeutics that inhibit gene splicing can be applied not only to other genes in MM but also more broadly to other hematological malignancies and solid tumors as well.
Table of Contents
Authors: A Vogel, J Bridgewater, R Kelley, H Klümpen, D Malka, J Primrose, L Rimassa, A Stenzinger, J Valle, M Ducreux, A Bazinet, H Kantarjian, S Labidi-Galy, M Rodrigues, J Sandoval, J Kurtz, F Heitz, A Mosconi, I Romero, U Denison, S Nagao, I Vergote, G Parma, T Nøttrup, E Rouleau, G Garnier, A El-Balat, C Zamagni, C Martín-Lorente, E Pujade-Lauraine, A Fiévet, I Ray-Coquard, H Tang, H Wang, Y Fang, J Zhu, J Yin, Y Shen, Z Zeng, D Jiang, Y Hou, M Du, C Lian, Q Zhao, H Jiang, L Gong, Z Li, J Liu, D Xie, W Li, C Chen, B Zheng, K Chen, L Dai, Y Liao, K Li, H Li, N Zhao, L Tan
Journal: Annals of Oncology (2023)
Amyloid fibril-based thixotropic hydrogels for modeling of tumor spheroids in vitro
Authors: Namrata Singh, Komal Patel, Ambuja Navalkar, Pradeep Kadu, Debalina Datta, Debdeep Chatterjee, Semanti Mukherjee, Ranjit Shaw, Nitisha Gahlot, Abhishek Shaw, Sachin Jadhav, Samir K. Maji
Journal: Biomaterials (2023)
H2O2-responsive polymer prodrug nanoparticles with glutathione scavenger for enhanced chemo-photodynamic synergistic cancer therapy
Authors: Guanchun Wang, Yue Su, Xinliang Chen, Yongfeng Zhou, Ping Huang, Wei Huang, Deyue Yan
Journal: Bioactive Materials (2023)

The combination of chemotherapy and photodynamic therapy (PDT) based on nanoparticles (NPs) has been extensively developed to improve the therapeutic effect and decrease the systemic toxicity of current treatments. However, overexpressed glutathione (GSH) in tumor cells efficiently scavenges singlet oxygens (1O2) generated from photosensitizers and results in the unsatisfactory efficacy of PDT. To address this obstacle, here we design H2O2-responsive polymer prodrug NPs with GSH-scavenger (Ce6@P(EG-a-CPBE) NPs) for chemo-photodynamic synergistic cancer therapy. They are constructed by the co-self-assembly of photosensitizer chlorin e6 (Ce6) and amphiphilic polymer prodrug P(EG-a-CPBE), which is synthesized from a hydrophilic alternating copolymer P(EG-a-PD) by conjugating hydrophobic anticancer drug chlorambucil (CB) via an H2O2-cleavable linker 4-(hydroxymethyl)phenylboronic acid (PBA). Ce6@P(EG-a-CPBE) NPs can efficiently prevent premature drug leakage in blood circulation because of the high stability of the PBA linker under the physiological environment and facilitate the delivery of Ce6 and CB to the tumor site after intravenous injection. Upon internalization of Ce6@P(EG-a-CPBE) NPs by tumor cells, PBA is cleaved rapidly triggered by endogenous H2O2 to release CB and Ce6. Ce6 can effectively generate abundant 1O2 under 660 nm light irradiation to synergistically kill cancer cells with CB. Concurrently, PBA can be transformed into a GSH-scavenger (quinine methide, QM) under intracellular H2O2 and prevent the depletion of 1O2, which induces the cooperatively strong oxidative stress and enhanced cancer cell apoptosis. Collectively, such H2O2-responsive polymer prodrug NPs loaded with photosensitizer provide a feasible approach to enhance chemo-photodynamic synergistic cancer treatment.
Early osteoimmunomodulation by mucin hydrogels augments the healing and revascularization of rat critical-size calvarial bone defects
Authors: Song Chen, Huan Wang, Dachuan Liu, Jianzhong Bai, Håvard Jostein Haugen, Bin Li, Hongji Yan
Journal: Bioactive Materials (2023)

The design principle of osteogenic bone grafts has shifted from immunological inertness to limiting foreign body response to combined osteoimmunomodulatory activity to promote high-quality endogenous bone regeneration. Recently developed immunomodulatory mucin hydrogels have been shown to elicit very low complement activation and suppress macrophage release and activation after implantation in vivo. However, their immunoregulatory activity has not yet been studied in the context of tissue repair. Herein, we synthesized mucin-monetite composite materials and investigated their early osteoimmunomodulation using a critical-size rat bone defect model. We demonstrated that the composites can polarize macrophages towards the M2 phenotype at weeks 1 and 2. The early osteoimmunomodulation enhanced early osteogenesis and angiogenesis and ultimately promoted fracture healing and engraftment (revascularization of the host vasculature) at weeks 6 and 12. Overall, we demonstrated the applicability of mucin-based immunomodulatory biomaterials to enhance tissue repair in tissue engineering and regenerative medicine.
Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia
Authors: Clement Larrue, Sarah Mouche, Shan Lin, Federico Simonetta, Nastassja K. Scheidegger, Laury Poulain, Rudy Birsen, Jean-Emmanuel Sarry, Kimberly Stegmaier, Jerome Tamburini
Journal: Leukemia (2023)

Abstract Mitochondrial metabolism recently emerged as a critical dependency in acute myeloid leukemia (AML). The shape of mitochondria is tightly regulated by dynamin GTPase proteins, which drive opposing fusion and fission forces to consistently adapt bioenergetics to the cellular context. Here, we showed that targeting mitochondrial fusion was a new vulnerability of AML cells, when assayed in patient-derived xenograft (PDX) models. Genetic depletion of mitofusin 2 (MFN2) or optic atrophy 1 (OPA1) or pharmacological inhibition of OPA1 (MYLS22) blocked mitochondrial fusion and had significant anti-leukemic activity, while having limited impact on normal hematopoietic cells ex vivo and in vivo. Mechanistically, inhibition of mitochondrial fusion disrupted mitochondrial respiration and reactive oxygen species production, leading to cell cycle arrest at the G 0 /G 1 transition. These results nominate the inhibition of mitochondrial fusion as a promising therapeutic approach for AML.
Antibody–drug conjugates: in search of partners of choice
Authors: Jesús Fuentes-Antrás, Sofia Genta, Abi Vijenthira, Lillian L. Siu
Journal: Trends in cancer (2023)

Antibody-drug conjugates (ADCs) have become a credentialled class of anticancer drugs for both solid and hematological malignancies, with regulatory approvals mainly as single agents. Despite extensive preclinical and clinical efforts to develop rational ADC-based combinations, to date only a limited number have demonstrated survival improvements over standard of care. The most appealing partners for ADCs are those that offer additive or synergistic effects on tumor cells or their microenvironment without unacceptable overlapping toxicities. Coadministration with antiangiogenic compounds, HER2-targeting drugs, DNA-damage response agents and immune checkpoint inhibitors (ICIs) represent active forerunners. Through the identification of targets with tumor-specific expression, improved conjugation technologies, and novel linkers and payloads offering superior therapeutic indices, the next generation of ADCs brings optimism to combinatorial approaches.
A microRNA signature to predict risk progression of vulvar lichen sclerosus to squamous cell carcinoma
Authors: Alessandro Borghi, Lucilla D’Abundo, Cristian Bassi, Laura Lupini, Valentina Tagliatti, Pierantonia Zedde, Giovanni Lanza, Roberta Gafà, Massimo Negrini, Monica Corazza
Journal: British Journal of Dermatology (2023)

DearEditor, Biomarkers useful for the identification of patients at risk of developing vulvar squamous cell carcinoma (VSCC) on a vulvar lichen sclerosus (VLS) background could lead to relevant prognostic advantages. To date, the development of such biomarkers is an unmet medical need. Among potential biomarker molecules, microRNAs (miRNAs) have been gaining attention. Involvement of miRNAs in vulvar carcinogenesis has been addressed with some evidence.1–6 We aimed to investigate whether miRNA expression could be useful to predict the progression from VLS to VSCC. This study, which was approved by the University-Hospital of Ferrara institutional review board (identification code 452/2021/Oss/AOUFe), included two different groups of formalin-fixed paraffin-embedded (FFPE) histologically proven VLS specimens: (i) 10 VLS samples that did not evolve towards carcinoma from patients with a mean clinical follow-up of 6 years, defined as VLS free from cancer (VLSfc); (ii) 13 samples including either VLS in which an invasive VSCC was histologically diagnosed in a subsequent biopsy, obtained after the first histological diagnosis of lichen sclerosus (n = 2, LIC19 and LIC20), or 11 VLS samples in which an invasive VSCC was diagnosed in the same surgical specimen. Both these sample types were defined as VLS cancer-associated (VLSca).
Advisory Board and Contents
Authors: Khandis Blake, Robert Brooks, Mats Küssner, Liila Taruffi, Elizabeth Margulis, J Mcauley, Lindsey Drayton, Danielle Loughlin, Rolf Van Der Sanden, Patrick Scheffmann, Ralph Adolphs, Renee Baillargeon, Nick Chater, Roshan Cools, Lila Davachi, Peter Dayan, Stanislas Dehaene, Daniel Dennett, Yadin Dudai, Andreas Engel, Martha Farah, Angela Friederici, Okihide Hikosaka, Ray Jackendoff, Philip Johnson-Laird, Nancy Kanwisher, Christof Koch, Marta Kutas, Nikos Logothetis, James Mcclelland, Earl Miller, Elizabeth Phelps, Russell Poldrack, Marcus Raichle, Trevor Robbins, Laurie Santos, Anthony Wagner, Vincent Walsh
Journal: Trends in Cognitive Sciences (2023)
IgE, IgE Receptors and Anti-IgE Biologics: Protein Structures and Mechanisms of Action
Authors: J.M. McDonnell, B. Dhaliwal, B.J. Sutton, H.J. Gould
Journal: Annual Review of Immunology (2023)

The evolution of IgE in mammals added an extra layer of immune protection at body surfaces to provide a rapid and local response against antigens from the environment. The IgE immune response employs potent expulsive and inflammatory forces against local antigen provocation, at the risk of damaging host tissues and causing allergic disease. Two well-known IgE receptors, the high-affinity FcεRI and low-affinity CD23, mediate the activities of IgE. Unlike other known antibody receptors, CD23 also regulates IgE expression, maintaining IgE homeostasis. This mechanism evolved by adapting the function of the complement receptor CD21. Recent insights into the dynamic character of IgE structure, its resultant capacity for allosteric modulation, and the potential for ligand-induced dissociation have revealed previously unappreciated mechanisms for regulation of IgE and IgE complexes. We describe recent research, highlighting structural studies of the IgE network of proteins to analyze the uniquely versatile activities of IgE and anti-IgE biologics.
Microenvironmental modulation in tandem with human stem cell transplantation enhances functional recovery after chronic complete spinal cord injury
Authors: Shogo Hashimoto, Narihito Nagoshi, Munehisa Shinozaki, Katsuyuki Nakanishi, Yu Suematsu, Takahiro Shibata, Momotaro Kawai, Takahiro Kitagawa, Kentaro Ago, Yasuhiro Kamata, Kaori Yasutake, Ikuko Koya, Yoshinari Ando, Aki Minoda, Tomoko Shindo, Shinsuke Shibata, Morio Matsumoto, Masaya Nakamura, Hideyuki Okano
Journal: Biomaterials (2023)

While rapid advancements in regenerative medicine strategies for spinal cord injury (SCI) have been made, most research in this field has focused on the early stages of incomplete injury. However, the majority of patients experience chronic severe injury; therefore, treatments for these situations are fundamentally important. Here, we hypothesized that environmental modulation via a clinically relevant hepatocyte growth factor (HGF)-releasing scaffold and human iPS cell-derived neural stem/progenitor cells (hNS/PCs) transplantation contributes to functional recovery after chronic complete transection SCI. Effective release of HGF from a collagen scaffold induced progressive axonal elongation and increased grafted cell viability by activating microglia/macrophages and meningeal cells, inhibiting inflammation, reducing scar formation, and enhancing vascularization. Furthermore, hNS/PCs transplantation enhanced endogenous neuronal regrowth, the extension of graft axons, and the formation of circuits around the lesion and lumbar enlargement between host and graft neurons, resulting in the restoration of locomotor and urinary function. This study presents an effective therapeutic strategy for severe chronic SCI and provides evidence for the feasibility of regenerative medicine strategies using clinically relevant materials.
IL-4 and IL-13: Regulators and Effectors of Wound Repair
Authors: Judith E. Allen
Journal: Annual Review of Immunology (2023)

Type 2 immunity mediates protective responses to helminths and pathological responses to allergens, but it also has broad roles in the maintenance of tissue integrity, including wound repair. Type 2 cytokines are known to promote fibrosis, an overzealous repair response, but their contribution to healthy wound repair is less well understood. This review discusses the evidence that the canonical type 2 cytokines, IL-4 and IL-13, are integral to the tissue repair process through two main pathways. First, essential for the progression of effective tissue repair, IL-4 and IL-13 suppress the initial inflammatory response to injury. Second, these cytokines regulate how the extracellular matrix is modified, broken down, and rebuilt for effective repair. IL-4 and/or IL-13 amplifies multiple aspects of the tissue repair response, but many of these pathways are highly redundant and can be induced by other signals. Therefore, the exact contribution of IL-4Rα signaling remains difficult to unravel.
Corrigendum to “Targeted delivery of hesperetin to cartilage to attenuates osteoarthritis by bimodal imaging with Gd2(CO3)3@PDA nanoparticles via TLR-2/NF-κB/Akt signaling” [Biomaterials 205 (2019)50–63]
Authors: Zhengxiao Ouyang, Chunfeng Liu, Tingting Tan, Juan Duan, Wanchun Wang, Xiaoning Guo, Qing Zhang, Zhihong Li, Qianli Huang, Pengcheng Dou, Tang Liu
Journal: Biomaterials (2023)
Prevalent Introgression Underlies Convergent Evolution in the Diversification of<i>Pungitius</i>Sticklebacks
Authors: Yu Wang, Yingnan Wang, Xiaoqi Cheng, Yongli Ding, Chongnv Wang, Juha Merilä, Baocheng Guo
Journal: Molecular Biology and Evolution (2023)

Abstract New mutations and standing genetic variations contribute significantly to repeated phenotypic evolution in sticklebacks. However, less is known about the role of introgression in this process. We analyzed taxonomically and geographically comprehensive genomic data from Pungitius sticklebacks to decipher the extent of introgression and its consequences for the diversification of this genus. Our results demonstrate that introgression is more prevalent than suggested by earlier studies. Although gene flow was generally bidirectional, it was often asymmetric and left unequal genomic signatures in hybridizing species, which might, at least partly, be due to biased hybridization and/or population size differences. In several cases, introgression of variants from one species to another was accompanied by transitions of pelvic and/or lateral plate structures—important diagnostic traits in Pungitius systematics—and frequently left signatures of adaptation in the core gene regulatory networks of armor trait development. This finding suggests that introgression has been an important source of genetic variation and enabled phenotypic convergence among Pungitius sticklebacks. The results highlight the importance of introgression of genetic variation as a source of adaptive variation underlying key ecological and taxonomic traits. Taken together, our study indicates that introgression-driven convergence likely explains the long-standing challenges in resolving the taxonomy and systematics of this small but phenotypically highly diverse group of fish.
Yam-derived exosome-like nanovesicles stimulate osteoblast formation and prevent osteoporosis in mice
Authors: Jin-Hyeon Hwang, Yu-Seong Park, Hyuk-Soon Kim, Dong-ha Kim, Sang-Hoon Lee, Chan-Hyeong Lee, Seung-Hoon Lee, Jung-Eun Kim, Sangkyu Lee, Ho Min Kim, Hyun-Woo Kim, Jihoon Kim, Wonhyo Seo, Hyo-Jung Kwon, Byoung-Joon Song, Do-Kyun Kim, Moon-Chang Baek, Young-Eun Cho
Journal: Journal of Controlled Release (2023)